Halogen-metal exchange reaction is widely used as a technique for substituting a halogen atom present in a halogenated organic compound into other substituent. As a reagent employed in the halogen-metal exchange reaction are exemplified Grignard reagents and organolithium reagents.
Since Grignard reagents have low reactivity in general, it is necessary to often use such reagents in an excess when reacted with an aryl chloride or an aryl bromide. Also, such reagents require a long reaction time. Therefore, reaction with the Grignard reagents is of no practical use from standpoint of industrial production (see Tetrahedron Letters, Vol. 40, pages. 4339-4342 (1999) by F. Trecourt, et al.) On the other hand, the Grignard reagents have a high reactivity for practical use to an aryl iodide, but it is troublesome to introduce an iodine atom in the way of synthetic route. The reaction using such Grignard reagents is, therefore, not desirable in view of industrial production (see Journal of Organic Chemistry, Vol. 57, pages 407-410 (1992) by Hisao Nishiyama, et al., Tetrahedron Letters Vol. 28, No. 47, pages 5845-5848 (1987) by Naomichi Furukawa, et al., and Journal of Organic Chemistry, Vol. 56, pages 5739-5740 (1991) by Richard M. Turner, et al.).
Organolithium reagents are widely used in halogen-metal exchange reaction, and can be also applied to a wide range of reaction substrates. However, thermostability of such organolithium compound itself or that of an intermediate lithio compound by-produced is generally not high. It is, therefore, essential to often carry out the reaction under the conditions of extreme low temperature which is unsuitable for industrial production (see. Journal of Medicinal Chemistry, Vol. 42, pages 1088-1099, (1999) by Tatsuzo Ukita, et al., Tetrahedron Letters, Vol. 37, No. 15, pages 2537-2540 (1996) by Dongwei Cai, et al., and Journal of Organic Chemistry, Vol. 58, pages 4382-4388 (1993) by Jun'ichi Uenishi et al.).
Further, exchange reactions of functional groups in iodo alkenes (see Journal of Organic Chemistry, Vol. 64, pages 1080-1081 (1999) by Mario Rottlander, et al.) and in bromoaryl compounds or bromoheteroaryl compounds (see Tetrahedron letters, Vol. 40, pages 7449-7453 (1999) by Mohamed Abarbri, et al.), using diisopropylmagnesium, are also known.